{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:23:37Z","timestamp":1785421417948,"version":"3.56.0"},"reference-count":67,"publisher":"Rockefeller University Press","issue":"4","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_184765"],"award-info":[{"award-number":["310030_184765"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_212192"],"award-info":[{"award-number":["310030_212192"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SwissLife","award":["1206"],"award-info":[{"award-number":["1206"]}]},{"name":"SwissLife","award":["1251"],"award-info":[{"award-number":["1251"]}]},{"name":"RyR1 Foundation"},{"DOI":"10.13039\/501100002426","name":"Italian Telethon","doi-asserted-by":"publisher","award":["ONLUS GGP19231"],"award-info":[{"award-number":["ONLUS GGP19231"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,4,1]]},"abstract":"<jats:p>RYR1 is the most commonly mutated gene associated with congenital myopathies, a group of early-onset neuromuscular conditions of variable severity. The functional effects of a number of dominant RYR1 mutations have been established; however, for recessive mutations, these effects may depend on multiple factors, such as the formation of a hypomorphic allele, or on whether they are homozygous or compound heterozygous. Here, we functionally characterize a new transgenic mouse model knocked-in for mutations identified in a severely affected child born preterm and presenting limited limb movement. The child carried the homozygous c.14928C&amp;gt;G RYR1 mutation, resulting in the p.F4976L substitution. In vivo and ex vivo assays revealed that homozygous mice fatigued sooner and their muscles generated significantly less force compared with their WT or heterozygous littermates. Electron microscopy, biochemical, and physiological analyses showed that muscles from RyR1 p.F4976L homozygous mice have the following properties: (1) contain fewer calcium release units and show areas of myofibrillar degeneration, (2) contain less RyR1 protein, (3) fibers show smaller electrically evoked calcium transients, and (4) their SR has smaller calcium stores. In addition, single-channel recordings indicate that RyR1 p.F4976L exhibits higher Po in the presence of 100 \u03bcM [Ca2+]. Our mouse model partly recapitulates the clinical picture of the homozygous human patient and provides significant insight into the functional impact of this mutation. These results will help understand the pathology of patients with similar RYR1 mutations.<\/jats:p>","DOI":"10.1085\/jgp.202313486","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T02:20:46Z","timestamp":1707531646000},"update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":7,"title":["A novel, patient-derived RyR1 mutation impairs muscle function and calcium homeostasis in mice"],"prefix":"10.1085","volume":"156","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5816-9158","authenticated-orcid":true,"given":"Sofia","family":"Benucci","sequence":"first","affiliation":[{"name":"Basel University Hospital 1 Departments of Biomedicine and Neurology, , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4333-2132","authenticated-orcid":true,"given":"Alexis","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Basel University Hospital 1 Departments of Biomedicine and Neurology, , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4971-9572","authenticated-orcid":true,"given":"Martina","family":"Franchini","sequence":"additional","affiliation":[{"name":"Basel University Hospital 1 Departments of Biomedicine and Neurology, , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-9567","authenticated-orcid":true,"given":"Lucia","family":"Ruggiero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Universit\u00e0 degli Studi di Napoli Federico II 2 Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, , Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9794-9245","authenticated-orcid":true,"given":"Dario","family":"Zoppi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05290cv24","id-type":"ROR","asserted-by":"publisher"}],"name":"Universit\u00e0 degli Studi di Napoli Federico II 2 Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, , Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3216-2560","authenticated-orcid":true,"given":"Rebecca","family":"Sitsapesan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford 3 Department of Pharmacology, , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-4985","authenticated-orcid":true,"given":"Chris","family":"Lindsay","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford 3 Department of Pharmacology, , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0189-6868","authenticated-orcid":true,"given":"Pawel","family":"Pelczar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02s6k3f65","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Transgenic Models, University of Basel 4 , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-7813","authenticated-orcid":true,"given":"Laura","family":"Pietrangelo","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology, University G. d\u2019Annunzio of Chieti-Pescara 5 DMSI, Department of Medicine and Aging Sciences and CAST, , Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0213-7591","authenticated-orcid":true,"given":"Feliciano","family":"Protasi","sequence":"additional","affiliation":[{"name":"Center for Advanced Studies and Technology, University G. d\u2019Annunzio of Chieti-Pescara 5 DMSI, Department of Medicine and Aging Sciences and CAST, , Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-9631","authenticated-orcid":true,"given":"Susan","family":"Treves","sequence":"additional","affiliation":[{"name":"Basel University Hospital 1 Departments of Biomedicine and Neurology, , Basel, Switzerland"},{"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Ferrara 6 Department of Life Science and Biotechnology, , Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8469-7065","authenticated-orcid":true,"given":"Francesco","family":"Zorzato","sequence":"additional","affiliation":[{"name":"Basel University Hospital 1 Departments of Biomedicine and Neurology, , Basel, Switzerland"},{"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Ferrara 6 Department of Life Science and Biotechnology, , Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"2024031415455643900_bib1","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.nmd.2017.05.016","article-title":"Common and variable clinical, histological, and imaging findings of recessive RYR1-related centronuclear myopathy patients","volume":"27","author":"Abath Neto","year":"2017","journal-title":"Neuromuscul. Disord."},{"key":"2024031415455643900_bib2","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1007\/s12079-018-0477-z","article-title":"Role of defective Ca2+ signaling in skeletal muscle weakness: Pharmacological implications","volume":"12","author":"Agrawal","year":"2018","journal-title":"J. Cell Commun. Signal."},{"key":"2024031415455643900_bib3","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/1750-1172-8-117","article-title":"Genotype-phenotype correlations in recessive RYR1-related myopathies","volume":"8","author":"Amburgey","year":"2013","journal-title":"Orphanet J. Rare Dis."},{"key":"2024031415455643900_bib4","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.pediatrneurol.2015.01.018","article-title":"A diagnostic dilemma in a family with cystinuria type B resolved by muscle magnetic resonance","volume":"52","author":"Astrea","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"2024031415455643900_bib5","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1085\/jgp.201210773","article-title":"Intracellular calcium movements during excitation-contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers","volume":"139","author":"Baylor","year":"2012","journal-title":"J. Gen. Physiol."},{"key":"2024031415455643900_bib6","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s12311-015-0687-3","article-title":"Consensus paper: Revisiting the symptoms and signs of cerebellar syndrome","volume":"15","author":"Bodranghien","year":"2016","journal-title":"Cerebellum"},{"key":"2024031415455643900_bib7","doi-asserted-by":"publisher","first-page":"21996","DOI":"10.1073\/pnas.0911496106","article-title":"Characterization and temporal development of cores in a mouse model of malignant hyperthermia","volume":"106","author":"Boncompagni","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024031415455643900_bib8","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1007\/s10974-009-9181-1","article-title":"Different fibre populations distinguished by their calcium transient characteristics in enzymatically dissociated murine flexor digitorum brevis and soleus muscles","volume":"30","author":"Calder\u00f3n","year":"2009","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2024031415455643900_bib9","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s12551-013-0135-x","article-title":"The excitation-contraction coupling mechanism in skeletal muscle","volume":"6","author":"Calder\u00f3n","year":"2014","journal-title":"Biophys. Rev."},{"key":"2024031415455643900_bib10","doi-asserted-by":"publisher","first-page":"4109","DOI":"10.1096\/fj.201600621R","article-title":"Orai1 enhances muscle endurance by promoting fatigue-resistant type I fiber content but not through acute store-operated Ca2+ entry","volume":"30","author":"Carrell","year":"2016","journal-title":"FASEB J."},{"key":"2024031415455643900_bib11","doi-asserted-by":"publisher","DOI":"10.21769\/BioProtoc.2237","article-title":"Evaluation of muscle performance in mice by treadmill exhaustion test and whole-limb grip strength assay","volume":"7","author":"Castro","year":"2017","journal-title":"Bio Protoc."},{"key":"2024031415455643900_bib12","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-1229-9_19","article-title":"Fitting and statistical analysis of single-channel records","volume-title":"Single-Channel Recording","author":"Colquhoun","year":"1995"},{"key":"2024031415455643900_bib13","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106491","article-title":"A necessary role of DNMT3A in endurance exercise by suppressing ALDH1L1-mediated oxidative stress","volume":"40","author":"Damal Villivalam","year":"2021","journal-title":"EMBO J."},{"key":"2024031415455643900_bib14","doi-asserted-by":"publisher","first-page":"16111","DOI":"10.1073\/pnas.1900544116","article-title":"BDNF is a mediator of glycolytic fiber-type specification in mouse skeletal muscle","volume":"116","author":"Delezie","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024031415455643900_bib15","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.cell.2016.08.075","article-title":"Structural basis for gating and activation of RyR1","volume":"167","author":"des Georges","year":"2016","journal-title":"Cell"},{"key":"2024031415455643900_bib16","doi-asserted-by":"publisher","first-page":"3193","DOI":"10.1529\/biophysj.104.048447","article-title":"Distinct effects on Ca2+ handling caused by malignant hyperthermia and central core disease mutations in RyR1","volume":"87","author":"Dirksen","year":"2004","journal-title":"Biophys. J."},{"key":"2024031415455643900_bib17","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1002\/ajmg.a.38418","article-title":"Treating pediatric neuromuscular disorders: The future is now","volume":"176","author":"Dowling","year":"2018","journal-title":"Am. J. Med. Genet. A."},{"key":"2024031415455643900_bib18","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1093\/hmg\/ddaa056","article-title":"Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous Ryr1 mutations","volume":"29","author":"Eckhardt","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"2024031415455643900_bib19","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1085\/jgp.201912333","article-title":"Extraocular muscle function is impaired in ryr3 \u2212\/\u2212 mice","volume":"151","author":"Eckhardt","year":"2019","journal-title":"J. Gen. Physiol."},{"key":"2024031415455643900_bib20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.83618","article-title":"Quantitative proteomic analysis of skeletal muscles from wild-type and transgenic mice carrying recessive Ryr1 mutations linked to congenital myopathies","volume":"12","author":"Eckhardt","year":"2023","journal-title":"Elife"},{"key":"2024031415455643900_bib21","doi-asserted-by":"publisher","first-page":"4769","DOI":"10.1113\/JP273550","article-title":"Dampened activity of ryanodine receptor channels in mutant skeletal muscle lacking TRIC-A","volume":"595","author":"El-Ajouz","year":"2017","journal-title":"J. Physiol."},{"key":"2024031415455643900_bib22","doi-asserted-by":"publisher","first-page":"2987","DOI":"10.1093\/hmg\/ddz092","article-title":"Quantitative RyR1 reduction and loss of calcium sensitivity of RyR1Q1970fsX16+A4329D cause cores and loss of muscle strength","volume":"28","author":"Elbaz","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2024031415455643900_bib23","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1093\/hmg\/ddz025","article-title":"Quantitative reduction of RyR1 protein caused by a single-allele frameshift mutation in RYR1 ex36 impairs the strength of adult skeletal muscle fibres","volume":"28","author":"Elbaz","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"2024031415455643900_bib24","doi-asserted-by":"publisher","first-page":"10331","DOI":"10.1074\/jbc.RA120.013846","article-title":"Bi-allelic expression of the RyR1 p.A4329D mutation decreases muscle strength in slow-twitch muscles in mice","volume":"295","author":"Elbaz","year":"2020","journal-title":"J. Biol. Chem."},{"key":"2024031415455643900_bib25","first-page":"181","article-title":"Calcium release from sarcoplasmic reticulum","volume-title":"Current Topics in Membranes and Transport","author":"Endo","year":"1985"},{"key":"2024031415455643900_bib26","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1146\/annurev.bb.18.060189.002001","article-title":"Biochemistry and biophysics of excitation-contraction coupling","volume":"18","author":"Fleischer","year":"1989","journal-title":"Annu. Rev. Biophys. Biophys. Chem."},{"key":"2024031415455643900_bib27","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1146\/annurev.ph.56.030194.002453","article-title":"Structure and development of E-C coupling units in skeletal muscle","volume":"56","author":"Franzini-Armstrong","year":"1994","journal-title":"Annu. Rev. Physiol."},{"key":"2024031415455643900_bib28","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1038\/nrneurol.2017.191","article-title":"Congenital myopathies: Disorders of excitation-contraction coupling and muscle contraction","volume":"14","author":"Jungbluth","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"2024031415455643900_bib29","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1750-1172-3-26","article-title":"Centronuclear (myotubular) myopathy","volume":"3","author":"Jungbluth","year":"2008","journal-title":"Orphanet J. Rare Dis."},{"key":"2024031415455643900_bib30","doi-asserted-by":"publisher","first-page":"355","DOI":"10.2170\/physiolsci.RP007706","article-title":"Electrophoretic separation of human skeletal muscle myosin heavy chain isoforms: The importance of reducing agents","volume":"56","author":"Kohn","year":"2006","journal-title":"J. Physiol. Sci."},{"key":"2024031415455643900_bib31","doi-asserted-by":"publisher","first-page":"6184185","DOI":"10.1155\/2018\/6184185","article-title":"A rare case of severe congenital RYR1-associated myopathy","volume":"2018","author":"Laforgia","year":"2018","journal-title":"Case Rep. Genet."},{"key":"2024031415455643900_bib32","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1007\/s13311-018-00677-1","article-title":"Ryanodine receptor 1-related myopathies: Diagnostic and therapeutic approaches","volume":"15","author":"Lawal","year":"2018","journal-title":"Neurotherapeutics"},{"key":"2024031415455643900_bib33","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s13395-020-00243-4","article-title":"Ryanodine receptor 1-related disorders: An historical perspective and proposal for a unified nomenclature","volume":"10","author":"Lawal","year":"2020","journal-title":"Skelet. Muscle"},{"key":"2024031415455643900_bib34","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s13395-014-0027-1","article-title":"Ca(2+) permeation and\/or binding to CaV1.1 fine-tunes skeletal muscle Ca(2+) signaling to sustain muscle function","volume":"5","author":"Lee","year":"2015","journal-title":"Skelet Muscle"},{"key":"2024031415455643900_bib35","doi-asserted-by":"publisher","first-page":"4164","DOI":"10.1073\/pnas.96.7.4164","article-title":"A mutation in the transmembrane\/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease","volume":"96","author":"Lynch","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2024031415455643900_bib36","doi-asserted-by":"publisher","first-page":"664618","DOI":"10.3389\/fneur.2021.664618","article-title":"Early findings in neonatal cases of RYR1-related congenital myopathies","volume":"12","author":"Mauri","year":"2021","journal-title":"Front. Neurol."},{"key":"2024031415455643900_bib37","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/(SICI)1098-1004(200005)15:5&lt;410::AID-HUMU2&gt;3.0.CO;2-D","article-title":"Ryanodine receptor mutations in malignant hyperthermia and central core disease","volume":"15","author":"McCarthy","year":"2000","journal-title":"Hum. Mutat."},{"key":"2024031415455643900_bib38","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/0304-4157(94)00014-5","article-title":"The role of Ca2+ ions in excitation-contraction coupling of skeletal muscle fibres","volume":"1241","author":"Melzer","year":"1995","journal-title":"Biochim. Biophys. Acta"},{"key":"2024031415455643900_bib39","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202012617","article-title":"Pre-assembled Ca2+ entry units and constitutively active Ca2+ entry in skeletal muscle of calsequestrin-1 knockout mice","volume":"152","author":"Michelucci","year":"2020","journal-title":"J. Gen. Physiol."},{"key":"2024031415455643900_bib40","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1038\/ncomms2496","article-title":"Enhanced dihydropyridine receptor calcium channel activity restores muscle strength in JP45\/CASQ1 double knockout mice","volume":"4","author":"Mosca","year":"2013","journal-title":"Nat. Commun."},{"key":"2024031415455643900_bib41","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000341","article-title":"Congenital myopathies in the adult neuromuscular clinic: Diagnostic challenges and pitfalls","volume":"5","author":"Nicolau","year":"2019","journal-title":"Neurol. Genet."},{"key":"2024031415455643900_bib42","doi-asserted-by":"publisher","first-page":"13485","DOI":"10.1038\/s41598-017-14081-w","article-title":"Exercise and high-fat feeding remodel transcript-metabolite interactive networks in mouse skeletal muscle","volume":"7","author":"P\u00e9rez-Schindler","year":"2017","journal-title":"Sci. Rep."},{"key":"2024031415455643900_bib43","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera: A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"2024031415455643900_bib44","doi-asserted-by":"publisher","first-page":"35358","DOI":"10.18632\/oncotarget.6139","article-title":"Age-dependent uncoupling of mitochondria from Ca2\u207a release units in skeletal muscle","volume":"6","author":"Pietrangelo","year":"2015","journal-title":"Oncotarget"},{"key":"2024031415455643900_bib45","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.abb.2018.12.017","article-title":"Muscle activity prevents the uncoupling of mitochondria from Ca2+ Release Units induced by ageing and disuse","volume":"663","author":"Pietrangelo","year":"2019","journal-title":"Arch. Biochem. Biophys."},{"key":"2024031415455643900_bib46","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s12576-009-0069-z","article-title":"The cell boundary theorem: A simple law of the control of cytosolic calcium concentration","volume":"60","author":"R\u00edos","year":"2010","journal-title":"J. Physiol. Sci."},{"key":"2024031415455643900_bib47","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1152\/physrev.1991.71.3.849","article-title":"Voltage sensor of excitation-contraction coupling in skeletal muscle","volume":"71","author":"R\u00edos","year":"1991","journal-title":"Physiol. Rev."},{"key":"2024031415455643900_bib48","doi-asserted-by":"publisher","first-page":"4636","DOI":"10.1093\/hmg\/ddv195","article-title":"Epigenetic changes as a common trigger of muscle weakness in congenital myopathies","volume":"24","author":"Rokach","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"2024031415455643900_bib49","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1186\/s12859-017-1934-z","article-title":"ImageJ2: ImageJ for the next generation of scientific image data","volume":"18","author":"Rueden","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2024031415455643900_bib50","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.73718","article-title":"Improvement of muscle strength in a mouse model for congenital myopathy treated with HDAC and DNA methyltransferase inhibitors","volume":"11","author":"Ruiz","year":"2022","journal-title":"Elife"},{"key":"2024031415455643900_bib51","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1083\/jcb.99.3.875","article-title":"Preparation and morphology of sarcoplasmic reticulum terminal cisternae from rabbit skeletal muscle","volume":"99","author":"Saito","year":"1984","journal-title":"J. Cell Biol."},{"key":"2024031415455643900_bib52","doi-asserted-by":"publisher","first-page":"e1495","DOI":"10.1212\/WNL.0000000000207723","article-title":"Long-term natural history of pediatric dominant and recessive RYR1-related myopathy","volume":"101","author":"Sarkozy","year":"2023","journal-title":"Neurology"},{"key":"2024031415455643900_bib53","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13395-015-0046-6","article-title":"Developmental myosins: Expression patterns and functional significance","volume":"5","author":"Schiaffino","year":"2015","journal-title":"Skelet. Muscle"},{"key":"2024031415455643900_bib54","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.str.2011.03.019","article-title":"A smoothed backbone-dependent rotamer library for proteins derived from adaptive kernel density estimates and regressions","volume":"19","author":"Shapovalov","year":"2011","journal-title":"Structure"},{"key":"2024031415455643900_bib55","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s12551-020-00610-x","article-title":"Excitation-contraction coupling in skeletal muscle: Recent progress and unanswered questions","volume":"12","author":"Shishmarev","year":"2020","journal-title":"Biophys. Rev."},{"key":"2024031415455643900_bib56","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1113\/jphysiol.1991.sp018481","article-title":"Sheep cardiac sarcoplasmic reticulum calcium-release channels: Modification of conductance and gating by temperature","volume":"434","author":"Sitsapesan","year":"1991","journal-title":"J. Physiol."},{"key":"2024031415455643900_bib57","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","article-title":"Cellpose: A generalist algorithm for cellular segmentation","volume":"18","author":"Stringer","year":"2021","journal-title":"Nat. Methods"},{"key":"2024031415455643900_bib58","doi-asserted-by":"publisher","first-page":"2337","DOI":"10.1152\/jappl.1993.75.5.2337","article-title":"Electrophoretic separation of rat skeletal muscle myosin heavy-chain isoforms","volume":"75","author":"Talmadge","year":"1993","journal-title":"J. Appl. Physiol."},{"key":"2024031415455643900_bib59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025740","article-title":"Disrupted membrane structure and intracellular Ca\u00b2\u207a signaling in adult skeletal muscle with acute knockdown of Bin1","volume":"6","author":"Tjondrokoesoemo","year":"2011","journal-title":"PLoS One"},{"key":"2024031415455643900_bib60","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.coph.2008.01.005","article-title":"Congenital muscle disorders with cores: The ryanodine receptor calcium channel paradigm","volume":"8","author":"Treves","year":"2008","journal-title":"Curr. Opin. Pharmacol."},{"key":"2024031415455643900_bib61","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1097\/00019052-200110000-00005","article-title":"Congenital myopathies and congenital muscular dystrophies","volume":"14","author":"Tubridy","year":"2001","journal-title":"Curr. Opin. Neurol."},{"key":"2024031415455643900_bib62","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1016\/j.bpj.2013.12.041","article-title":"FKBP12.6 activates RyR1: Investigating the amino acid residues critical for channel modulation","volume":"106","author":"Venturi","year":"2014","journal-title":"Biophys. J."},{"key":"2024031415455643900_bib63","doi-asserted-by":"publisher","first-page":"11793","DOI":"10.1038\/s41598-021-91191-6","article-title":"Automatic and unbiased segmentation and quantification of myofibers in skeletal muscle","volume":"11","author":"Waisman","year":"2021","journal-title":"Sci. Rep."},{"key":"2024031415455643900_bib64","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.202112976","article-title":"Acute exposure to extracellular BTP2 does not inhibit Ca2+ release during EC coupling in intact skeletal muscle fibers","volume":"154","author":"Wei-LaPierre","year":"2022","journal-title":"J. Gen. Physiol."},{"key":"2024031415455643900_bib65","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1083\/jcb.101.2.618","article-title":"Co-Expression of multiple myosin heavy chain genes, in addition to a tissue-specific one, in extraocular musculature","volume":"101","author":"Wieczorek","year":"1985","journal-title":"J. Cell Biol."},{"key":"2024031415455643900_bib66","doi-asserted-by":"publisher","first-page":"D520","DOI":"10.1093\/nar\/gky949","article-title":"Protein Data Bank: The single global archive for 3D macromolecular structure data","volume":"47","author":"wwPDB consortium","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2024031415455643900_bib67","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1080\/15216540601187803","article-title":"Functional effects of mutations identified in patients with multiminicore disease","volume":"59","author":"Zorzato","year":"2007","journal-title":"IUBMB Life"}],"container-title":["Journal of General Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313486\/1925593\/jgp_202313486.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jgp\/article-pdf\/doi\/10.1085\/jgp.202313486\/1925593\/jgp_202313486.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T11:47:51Z","timestamp":1710416871000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jgp\/article\/156\/4\/e202313486\/276594\/A-novel-patient-derived-RyR1-mutation-impairs"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":67,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,4,1]]}},"URL":"https:\/\/doi.org\/10.1085\/jgp.202313486","relation":{},"ISSN":["0022-1295","1540-7748"],"issn-type":[{"value":"0022-1295","type":"print"},{"value":"1540-7748","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"article-number":"e202313486"}}